1. Technical Field
The present invention relates to a therapeutic method and a diagnostic method using antibodies that bind to ganglioside GM2 antigen. The invention also relates to a therapeutic agent and a diagnostic agent that comprise antibodies that bind to ganglioside GM2 antigen as active ingredients.
2. Background Art
Gangliosides are a type of glycolipids composed of an extracellular sugar chain moiety containing a sialic acid, and a ceramide embedded in the lipid bilayer, and are expressed in a variety of patterns that varies according to cell type, organs, and animal species (Non-Patent Literature 1). It has been revealed that gangliosides have a wide range of biological functions, including intercellular recognition, control of cell proliferation via interaction with extracellular matrixs, and cell differentiation (Non-Patent Literatures 2 and 3).
Gangliosides are classified according to the patterns and the number of the sialic acid binding, and the presence or absence of N-acetylgalactosamine (GalNAc) and galactose (Gal) bound to the non-reducing end. GM2 is a member of ganglioside with the GalNAcβ1-4(SAα2-3)Galβ1-4Glcβ1-1 Ceramide sugar chain structure.
It has been reported that ganglioside expression undergoes quantitative and qualitative changes with progression of cancer cells (Non-Patent Literature 4). It is also known that there is hardly any GM2 expression in normal cells, whereas high GM2 expression is observed in tumors such as lung cancer, neuroblastoma and glioma (Non-Patent Literatures 4 and 5). This has made GM2 an attractive target antigen in antibody cancer treatment.
Mesothelioma, also called a coated mesothelial tumor or mesothelial tumor, is a type of tumor that develops from mesothelium (such as pleura, peritonea and pericardium) of mesoderm origin, and is classified into localized benign tumors and diffuse malignant tumors. A form of malignant mesothelioma that occurs in pleura is malignant pleural mesothelioma (hereinafter, abbreviated to MPM in some cases).
MPM is a form of cancer that develops from the mesothelial cells of the thoracic cavity and is characterized by high growth rate, often accompanied by pleural effusion (Non-Patent Literature 6). Difficulty in breathing, short breath and cheat pain are some of the symptoms of MPM, and the quality of life (QOL) of the patients are lowered. Asbestos, iron, and simian virus 40 (SV40) are known examples of the causative substances of MPM (Non-Patent Literatures 7 and 8).
In particular, exposure to asbestos has been considered to be heavily associated with the onset of MPM, and people with a history of asbestos exposure are at significantly increased risk of MPM onset. Japan has imported and used a high volume of asbestos between 1970 and 1980 (Non-Patent Literature 9). Because the latency period of MPM is believed from 30 to 40 years after asbestos exposure, the morbidity rate of MPM in Japan is expected to greatly increase from 2010 to 2020.
Though the only treatment for MPM is the removal of tumor at early stages of onset, the disease is often found at the developed stages in the clinic. Further, MPM does not respond to common chemotherapy and radiation therapy, and has very poor prognosis with an average survival time of about 1 year from the onset. Accordingly, there is a need for a therapeutic method that can improve the prognosis of the disease.